Early acquisition of bowel segment-specific Bcl-2 homolog expression profiles during development of the human ileum and colon

The adult small and large intestines display distinct expression profiles o f Bcl-2 homologs, known regulators of apoptosis. This is thought to indicat e that control mechanisms of intestinal apoptosis are gut segment-specific. Little is known on the expression of Bcl-2 homologs during gut development . In man, intestinal features and functions are acquired largely by mid-ges tation (18-20 wks); the question whether segment-specific controls of intes tinal apoptosis are also acquired early during development remains open. In the present study, we approached this by investigating the expression of s ix Bcl-2 homologs (Bcl-2, Bcl-XL, Mcl-1, Bax, Bak, Bad), and one nonhomolog ous associated molecule (Bag-l), during development of the human ileum and colon (12-20 wks of gestation). Beginning at 18 wks, we found that the epit helial localization of Bcl-2 homologs displayed differential patterns (or g radients) in both the ileum and colon; however, the patterns of some of the homologs differed between the two segments. For instance, Bag-1 and Bcl-2 exhibited crypt-villus decreasing gradients of expression in the ileum but not in the colon, whereas Mcl-1 displayed differing compartimentalizations between the two segments. Further analyses indicated that the steady-state expression levels of Bcl-2 homologs underwent modulations between 12 and 20 wks; however, the observed developmental profiles contrasted significantly between the two segments. For example, Bcl-2, Bag-1 and Bak levels increas ed in the colon, but the levels of these same homologs decreased in the ile um. Furthermore, by 18-20 wks, we found that the expression levels of each Bcl-2 homolog analyzed differed greatly between the ileum and colon. Altoge ther, these data indicate that the expression of Bcl-2 homologs is modulate d differentially during human gut development in order to establish, by mid gestation, distinct expression profiles for the small and large intestines. This in turn suggests that gut segment-specific control mechanisms of huma n intestinal apoptosis are acquired early during fetal life.